Abstract: L-asparaginase has been used as an effective antineoplastic agent. Asparaginases are the cornerstones of treatment protocols for acute lymphoblastic leukemia (ALL), it has been an integral part of combination chemotherapy protocols of pediatric acute lymphoblastic leukemia for almost 3 decades and in the majority of adult treatment protocols. The clinical action of this enzyme is attributed to the reduction of L-asparagine, since tumor cells unable to synthesize this amino acid are selectively killed by L-asparagine deprivation. However, L-asparaginase can cause hypersensitivity in the long-term used, leading to allergic reactions and anaphylaxis. Hence, studies are continued and focused on abatement of immune reactivity either by modifying the L-asparaginase using pegylation or by the screening of soil samples from various sources for isolation of potential microbes which have the ability to produce the desired enzyme. The search for other L-asparaginase sources, can lead to an enzyme with less adverse effects. The discovery of new L-asparaginase serologically different but having similar therapeutic effects is highly desirable.